The neuropharmacological effects of alcohol are known to vary by limb of the blood alcohol curve, yet human laboratory studies of alcoholism pharmacotherapies have largely failed to consider limb of intoxication when examining medication effects on subjective responses to alcohol. This study examined the effects of naltrexone compared to placebo on subjective responses to alcohol at the descending limb of the blood alcohol curve following a controlled intravenous (IV) alcohol administration. Non‐treatment‐seeking hazardous drinkers (n = 38) completed two double‐blind counterbalanced IV alcohol challenge sessions, one after taking naltrexone (50 mg) for three days and one after taking a placebo for three days. During each session, participants reported on subjective responses to alcohol during the descending limb of the blood alcohol curve. Analyses revealed significant main effects of naltrexone, reflecting significantly decreased alcohol‐induced stimulation, craving, vigor, positive mood, and alcohol “high” and increased tension as compared to placebo. These findings suggest that naltrexone may exert some of its therapeutic effects via alterations to experiential aspects of intoxication during the descending limb of alcohol intoxication. Additionally, these results highlight the potential utility of considering limb of blood alcohol curve when examining the mechanisms of action of pharmacotherapies thought to alter subjective responses to alcohol.